Methods and apparatus for treatment of a body cavity or lumen

ABSTRACT

Methods and apparatus for the treatment of a body cavity or lumen are described where a heated fluid and/or gas may be introduced through a catheter and into treatment area within the body contained between one or more inflatable/expandable members. The catheter may also have optional pressure sensing elements which may allow for control of the pressure within the treatment zone and also prevent the pressure from exceeding a pressure of the inflatable/expandable members to thereby contain the treatment area between these inflatable/expandable members. Optionally, a chilled or room temperature fluid such as water may then be used to rapidly terminate the treatment session.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/306,076 filed Nov. 29, 2011 (now U.S. Pat. No. 9,427,556), which is acontinuation of PCT International Application No. PCT/US2010/036947filed Jun. 1, 2010, which claims priority to U.S. ProvisionalApplication No. 61/217,537 filed Jun. 1, 2009; 61/277,770 filed Sep. 30,2009; and 61/337,648 filed Feb. 11, 2010, each of which is incorporatedherein by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to medical devices. In particular, thepresent invention relates to methods and apparatus for therapeuticdevices capable of exposing areas of the body to elevated or decreasedtemperatures, in a highly controlled manner.

BACKGROUND OF THE INVENTION

In the last few decades, therapeutic intervention within a body cavityor lumen has developed rapidly with respect to delivery of energy viaradio frequency ablation. While successful in several arenas, radiofrequency ablation has several major downsides, including incompleteablation, frequent lack of visualization during catheter insertion,potential for overlap during treatment (with some areas receiving twiceas much energy as other areas), charring of tissues and requirements forfrequent debridement, frequent requirements for additional doses ofenergy after debridement, and potential perforation of body cavity orlumen due to the rigidity of the RF electrodes.

The current state of the art would benefit from minimally invasivedevices and methods which deliver thermal energy to a desired area orextract energy from a desired area, in a consistent, controlled mannerthat does not char or freeze tissues or create excessive risk ofunwanted organ or lumen damage.

SUMMARY OF THE INVENTION

When bodily tissues are exposed to even slightly elevated temperatures(e.g., 42 degrees C. or greater), focal damage may occur. If the tissuesare exposed to temperatures greater than, e.g., 50 degrees C., for anextended period of time, tissue death will occur. The energy deliveredby RF can then be excessive while a more controlled treatment can beachieved with heated fluids and/or vapors.

Generally, devices for delivering controlled treatment may comprise asource for a heated fluid and/or gas, e.g., hot water/steam, one or morepumps to deliver said hot water/steam, a catheter having one or morelumens defined therethrough and also having one or more ports to deliveror circulate the heated fluid and/or gas, e.g., hot water and/or vapor,to a controlled site in a controlled manner. The catheter may also haveoptional pressure sensing elements. The optional pressure sensingelements may allow the operator to monitor and/or control the pressurewithin the treatment zone and also prevent the pressure from becomingtoo high. The treatment site may be delineated by inflatable orexpandable members which are pressurized or expanded to a targetpressure to form a seal with the body cavity/lumen. The heated fluidand/or gas may then be delivered to the area contained by theinflatable/expandable members at a pressure that is less than that ofthe inflatable/expandable members thereby effectively containing thetreatment area between these inflatable/expandable members. Optionally,a chilled or room temperature fluid such as water may then be used torapidly terminate the treatment session.

The catheter having the inflatable/expandable members and optionalpressure-sensing elements may be fitted within the lumen of an endoscopeor other visualization device allowing the therapy to be delivered underdirect visualization. In addition to direct visualization, this advanceallows the scope to function as an insulator for the treatment catheter,thereby preventing unwanted exposure of body cavities/lumens to theelevated temperatures found in the heated fluid and/or gas coursingwithin the treatment catheter.

Generally, the heated fluid and/or gas may be heated to a temperature ofbetween, e.g., 50 and 100 degrees Celsius. Exposure to these lesselevated temperatures may allow for more controlled tissue damage andmay obviate issues typically associated with the higher energy forms oftreatment. It is understood and known in the art that the lower thetemperature, the longer the dwell/treatment time needed. One treatmentmodality may be to deliver the heated fluid and/or gas at a temperatureof, e.g., about 70 degrees C. for 5 minutes. Another modality may be totreat the tissue with the heated fluid and/or gas at a temperature of,e.g., 90 degree C. for 30 secs.

Among other features, the system may also include 1) the ability tothoroughly treat the treatment area due to the use of confiningballoon(s) and/or use of an umbrella-like seal and use of a pressurizedheated fluid and/or gas as the energy delivery medium, 2) the ability totreat relatively large areas in a very controlled manner due to theadjustable relationship between the two treatment-area defininginflatable/expandable components (e.g. balloon(s) and/or anumbrella-like seal), 3) the ability to form a fluid and/or gas-tightseal between the balloon(s) (and/or an umbrella-like seal) due to thecatheter for the distal balloon traveling within the lumen of theproximal balloon catheter (avoidance of leakage around the cathetersthat the balloons can seal about), 4) the optional ability to monitorand control the pressure within the treatment area to ensure that thetreatment area is not exposed to excessive pressures and that thepressure in the treatment area is prohibited from exceeding a pressureof the treatment area defining balloons, 5) the ability to ablate to acontrolled depth in a reliable manner due to the lower energy and longerexposure times which allow the submucosa to cool itself with incomingblood flow, 6) the optional ability to fit within a working channel ofan endoscope so that the device need not be inserted in a blind manner,7) the ability to combine thermal or cooling therapy with delivery ofactive agents (e.g., anesthetic for pre-treatment of the target area ora chemotherapeutic for the treatment cancer or precancerous lesions,etc.), 8) the ability to fill the treatment defining area with fluid(e.g. cool, warm or room temperature fluid) capable of neutralizing thethermal or cooling energy in the treatment area in order to preventpotential damage caused by balloon rupture or seepage around the balloonand/or expandable member, 9) the ability to pre-chill (or pre-warm) thetreatment area so that the submucosal tissues can be protected againstthe elevated (or cooling) temperature to which the lumen or bodily organis being exposed, 10) the ability to adjust the treatment temperaturetime and/or temperature, 11) the ability to have modular, automated orsemi-automated components and controls for handling the cooling,heating, inflations, deflations, infusions and/or extractions, 12) theability to treat through the working channel of an endoscope oralongside an endoscope, 13) the ability to treat through a variety ofendoscopes, e.g. nasal, gastrointestinal, esophageal, etc., 14) theability to use off-the-shelf and/or disposable components to handle thefluid and pressure controls, or to use an automated or semi-automatedsystem.

Additionally, the system may also incorporate features that may allowfor efficacious therapy. For example, the system may utilize a sub-zerodegrees Celsius temperature fluid lavage. This cold lavage may allow formuch better control than charring and heating of the tissue and insteadmay provide a consistent depth of ablation in a manner that allows forrapid recovery and minimal post-operative pain (as opposed to heatingmethods). In addition, by using lavage of a fluid rather than cryogenicsprays (e.g., sprays which rely on the judgment of the user fordetermining time of spray application or spray location, etc.) thepotential for over-ablation may be avoided. Also, the relatively coldercryogenic sprays have been found, in many cases, to result in damage tothe endoscope while the higher temperatures possible with the systemdescribed herein (e.g., anywhere from −5 degrees Celsius to −80 degreesCelsius) is much less likely to damage the delivery equipment.

Secondly, the apparatus may utilize an umbrella-like element in thegastric space to allow for ablation of tissue regions, such as the loweresophageal sphincter at the gastroesophageal junction. This ablation isgenerally difficult to perform using balloon-based ablation technologiesdue to the expansion of the sphincter into the stomach. By utilizing anexpandable, umbrella-like structure to form a firm seal at this sitewhile allowing the ablation fluid and/or gas (heated or chilled) tocontact the entire gastroesophageal junction. In addition, aspring-loaded element or other external force mechanism may beincorporated to provide for steady pressure and a firm seal against thestomach lining.

The apparatus may also be utilized with or without a balloon in bodylumens or cavities that can be otherwise sealed. For example, ahypothermic fluid lavage of the uterus may be accomplished byintroducing a subzero (Celsius) fluid into the uterus via cannulation ofthe uterus with a tube or cannula. If the tube is of sufficientdiameter, backflow of the hypothermic lavage into the cervix and vaginamay be prevented without the need for a balloon to contain the fluid.Use of balloons may be avoided for this particular type of application.In utilizing a hypothermic lavage, a fluid may be used that remainsfluid even at subzero temperatures. This fluid may then circulated inthe lumen (with or without a balloon) in order achieve ablation.

In using a hypothermic fluid rather than a gas, a greater thermal loadcan be repeatedly extracted from the tissue under controlled physiologicconditions using a liquid beyond the thermal load which may be extractedusing a compressed gas. In addition, the pressure associated withrelease of a compressed gas into an excluded space may potentiallydamage tissue and may be difficult to control with respect to pressureand temperature. A fluid lavage, on the other hand, may be controlledbased on temperature and pressure to provide a repeatable effect on thetarget organ. Compressed gas or other rapid cooling mechanisms, though,may be utilized in combination with this therapy in order to chill asolution to subzero temperatures after introduction into the body. Inthis variation, the biocompatible fluid capable of retaining fluidcharacteristics in a subzero state, or “anti-freeze solution”, may beinfused into the lumen or cavity after which the cooling probe may beintroduced. Heat may be drawn from the anti-freeze solution until thedesired hypothermic ablation temperature has been achieved for thedesired duration of time. Fluid may or may not be circulated during thisprocess via a pump or agitating element within the catheter in order toimprove distribution of the ablative fluid.

In yet another variation, the treatment fluid may function to expand theuterus for consistent ablation, function to distribute the cryoablativefreezing more evenly throughout the uterus, and potentially function toprevent ice formation at the surface of the lumen or body cavity. In theuterus, for example, this layer of ice that may form on the surface ofthe endometrium is highly insulating and may prevent transmission of thecryoablative freeze zone to deeper surfaces requiring a longer treatmentwith potentially erratic effects. The apparatus may be used with, forexample, lipophilic, hydrophilic or amphipathic solutions with thelatter two being having the ability to remove any aqueous fluid from thesurface of the target cavity or lumen which may interfere withconduction of the heat from the target tissues into the cryoablativefluid.

Additionally and/or alternatively, the apparatus and methods describedherein may be used as an adjunct to other treatments, such as the HerOption® therapy (American Medical Systems, Minnetonka, Minn.), byutilizing a lavage of the target cavity or lumen such as the uterus withthe aqueous anti-freeze solution either prior to or during treatment inorder to provide superior transmission of cryoablation with otherexisting cryoprobes without creation of the insulating ice layer at thesurface. Moreover, lavage of the target lumen or cavity with abiocompatible antifreeze solution may be performed to improvetransmission of the cryoablative effect as an adjunct to any cryotherapytreatment anywhere in the body where applicable. As described herein,the cryoablative fluid may also be introduced and/or lavaged within thetarget lumen or body cavity within a balloon which may be expanded tocontact the walls of the lumen or body cavity. The cryoablativetreatment fluid may be actively lavaged in and out of the balloon and/ordeeply chilled by a cryoprobe within the balloon after introduction intothe body cavity or lumen. Moreover, the anti-freeze solution may alsocomprise various salts and/or other biocompatible molecules capable ofdriving the freezing temperature of the solution below, e.g., −10degrees Celsius. Additionally, the fluid may be capable of resistingfreezing even at a temperature of, e.g., −50 degrees Celsius. Acombination of salts, alcohols, glycols and/or other molecules may beused to provide this resistance to freezing in an aqueous solution.

In yet another variation, a cryoprobe with, e.g., a protective cageand/or a recirculator/fluid agitator, may be utilized to ensure that thehypothermic fluid is evenly distributed. The cage may be configured intovarious forms so long as it exposes the fluid to the surface of thecryoprobe while preventing direct contact of the cryoprobe with the wallof the lumen or cavity to be ablated (such as a uterus). A recirculatormay comprise, e.g., a stirring element at the tip of the cryoprobe, anintermittent or continuous flow system or other fluid movementmechanism.

BRIEF DESCRIPTION OF THE DRAWINGS

For the purposes of the drawings and preferred embodiments, applicationto the esophagus will be shown. However, the apparatus and methods maybe applied to any body cavity/lumen which may be visualized with anendoscope or other visualization mechanism.

FIG. 1 shows an example of a device advanced through an endoscope, e.g.,nasally or orally inserted scope.

FIG. 2 shows an example of a device advanced through the working channelof nasal endoscope.

FIG. 3 shows an example of a device attached to a logic controller.

FIG. 4 shows an example of a device placed through working channel ofnasal endoscope and deployed within an esophagus for treatment.

FIG. 5 shows an example of a device advanced alongside an endoscope.

FIGS. 6A to 6C show a device being introduced through an endoscope anddeployed for treatment within the esophagus.

FIGS. 7A to 7C show examples of a device introduced through an endoscopefor insertion within a bladder.

FIGS. 8A to 8C show examples of a device preparing the treatment areawith a pre-treatment lavage prior to treatment.

FIG. 9 shows an example of a distal occlude having an umbrella-likeshape deployed in proximity to a gastroesophageal junction fortreatment.

FIG. 10 shows another example of an endoscopic balloon sheath having adistal occluder expanded distal to gastroesophageal junction fortreatment.

FIG. 11 shows another example where the treatment fluid is introducedbetween the deployed balloons for treatment.

FIGS. 12A and 12B shows another example of a single balloon device forablation treatment within the uterus and/or endometrial lining.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 shows a perspective view of one example of the treatment assembly10 positioned within a working channel 14 of an endoscope 12 (e.g.,orally or nasally insertable scope). In this example, the treatmentdevice 16 itself may utilize a first catheter 18 having an inflatable orexpandable balloon member 22 and a second catheter 20 that may slidefreely with respect to the first catheter 18 and also having aninflatable balloon member 24 at its distal end. The first catheter 18 aswell as second catheter 20 may have a fluid and/or gas tight seal 30formed at the proximal end of the catheters. The inflatable and/orexpandable members 22, 24 (shown in this example as inflated balloons)may be pressurized to effectively and safely occlude the lumen. Theballoons may be filled with chilled or room temperature fluid to preventpossible damage caused by balloon rupture or seepage around the balloon.Pressure within the inflatable or expandable balloon members may also bemonitored to ensure that a tight seal has been formed within the lumenor body cavity.

Additionally, the fluid may be introduced into the treatment areathrough a fluid and/or gas port 28 and into the lumen of the catheterwhich terminates with the proximal balloon 22 and leaves the catheterthrough perforations or holes 32 within the second catheter 20 whichterminates in the distal balloon 24, although this flow path may easilybe reversed if necessary. Alternatively, one or more ports can bedesigned into the lumen between the distal 24 and proximal 22 balloons,such that the heated or cooling fluid exits one or more ports 32 in thelumens near the distal balloon 24, and is then evacuated in a port orports designed within the lumen of the first catheter 18 nearest theproximal balloon 22. In this variation, the endoscope 12 may insulatethe catheters allowing the catheters to be much smaller than would beotherwise possible and allowing it to fit within the working channel 14of a standard endoscope 12. One or more pressure sensors may be used todetect both inflation pressures of the balloons and/or the pressure seenby the body cavity/lumen that is exposed to the treatment fluid/vapor.In the manner, fluid/vapor flow may be controlled by the pressuresensing elements within the body cavity/lumen to ensure that safepressures are never exceeded. Manual controls may be used for creationand/or maintenance of these pressures (e.g. syringes with stopcocks) orautomated and/or semi-automated systems can be used as well (e.g. pumpswith PID loops and pressure sensing interconnectivity. Although thefluid and/or gas for tissue treatment may be heated or chilled prior tointroduction into the treatment area in contact with the tissue, thefluid and/or gas may alternatively be heated or chilled afterintroduction into the treatment area and already in contact with thetissue.

FIG. 2 shows an example where the second catheter 20 and distal balloonmember 24 is slidable relative to the proximal balloon 22. This examplesillustrates the endoscope inserted through the nasal cavity and advancedthrough the esophagus ES where the catheters 18, 20 may comprise singleor multi-lumen catheters having inflation lumens for the distal 24 andproximal 22 inflatable/expandable elements, infusion port and extractionport. At least one of the catheters may be fitted with either a pressuretransducer 42 or a lumen to carry the pressure signal from the treatmentarea back to the controller or dial gauge. Pressure sensing may beaccomplished through a small, air capsule proximal to the distal balloon24, but within the treatment area. Both of the balloons 22, 24 may beinflated along the esophagus ES in the proximity to the gastroesophagealjunction GJ proximal to the stomach ST to create a treatment space 40which encompasses the tissue region to be treated.

In an alternative embodiment, an extraction lumen may be omitted as apreset dose of heated fluid and/or gas may be delivered, allowed todwell and then either extracted through the same lumen or renderedharmless with the infusion of cold fluid. This treatment algorithm wouldprovide an even simpler therapy and would rely on the exclusion of acertain area and exposure of that area to a fluid or vapor with thedesired energy. Infusion of the fluid or vapor may be controlled toensure that the treatment area is not exposed to excessive temperatures.

FIG. 3 shows another example where the treatment assembly 10 may be incommunication with a controller 50, such as a logic controller.Controller 50 may control certain parameters such as infusion pressure54 of the fluid as well as fluid temperature 56 and it may be coupled tothe assembly by one or more cables 52. The pressure in the treatmentarea, the elapsed time, the temperature of the fluid, and the extractionrate may also be monitored and controlled.

FIG. 4 shows a detail view of the treatment area 40 defined, in thiscase, by two balloons 22, 24. The first catheter 18 may open into thelumen just after the proximal balloon 22 and this catheter 18 may beinserted along with or prior to insertion of the second catheter 20. Thefirst catheter 18 internal diameter is greater than the outer diameterof the second catheter allowing for fluid (and/or vapor) to be infusedor extracted around the outer diameter of the second catheter 20. Thesecond catheter 20 a first lumen for balloon inflation and a secondlumen for evacuating the treatment region 40. With the balloons inflatedinto contact against the esophagus ES, the treatment area 40 mayencompass the tissue region to be treated, e.g., a lesion 60 such asBarrett's esophagus or esophageal cancer lesion and the distal end ofthe endoscope 12 may be positioned into close proximity to proximalballoon 22 and the treating fluid and/or gas 66 may be infused throughthe annular lumen 70 defined through first catheter 18 and betweensecond catheter 20 such that the fluid 66 may enter through opening 62into the treatment region 40 while contained by the balloons. Oncetreatment has been completed, the fluid may be evacuated 68 through oneor more openings 64 located along the second catheter 20 proximal todistal balloon 24 and proximally through the second catheter 20 throughthe evacuation lumen 72. As previously mentioned, a pressure sensor 42(e.g., pressure measuring air capsule) may be positioned along eitherthe first 18 and/or second 20 catheter for sensing the variousparameters. Additionally, the treatment fluid and/or gas may include anynumber of fluids, vapors, or other chemically active (e.g.,chemotherapeutic) or inactive compounds for additional treatments to thetissue.

In the event that the treatment is provided by a simple timed dwell, theextraction 72 and infusion 70 lumens may not both be utilized. Thepressure sensing element 42 (solid-state, piezoelectric, or othermethod) may be located on either the first or second catheters and thesecond catheter and may comprise a simple slidable balloon. A pressuresensor for the treatment may omitted so long as the pressure can becontrolled by other mechanisms, e.g., a check valve or a simple gravityfluid column. An active pressure measurement, though, may ensure thatsafe pressures are not being exceeded.

The second catheter 20 may fit easily within the first catheter 18 andmay be slid inside the first catheter 18 until its distal balloon 24 isdistal to the first balloon 22. The distal balloon 24 may then beinflated just beyond the distal portion of the treatment area 40 and theendoscope 12 may be pulled back. The most proximal extent of the lesion60 may then be identified and the proximal balloon 22 may be inflatedproximal to this area. Once the treatment area 40 has been enclosed(which may be verified by infusing fluid 66 and/or vapor undervisualization and observing the seal around the balloon, balloons and/orexpandable member) the lumen or body cavity may then be filled with thetreatment fluid and/or vapor to a safe pressure. The fluid and/or vapormay also contain active agents (e.g. chemotherapeutic and/or anestheticagents) and comprise more than simply an inactive fluid and/or vapor.Options would be for the active agents to be delivered prior to, duringand/or post treatment of the heating (or cooling) fluid and/or vapor.

As the treatment assembly 16 does not contain the treatment fluid orvapor within a balloon(s) or expandable member and allows it to freelyflow over the treatment area, the therapy may be applied consistentlyleaving no areas left untreated (as is frequently seen with ballooninfusion-based or RF therapies). Additionally, treatment may beaccomplished with a heated fluid (rather than a high energy electrode orexcessively hot vapor) or a more controlled treatment can be achievedthrough the use of a relatively cooler fluid with a longer treatmenttime. In addition, the esophagus ES is a fluid transport type organ(lumen) and may be more compatible to fluid based therapies than withRF-based therapies. It is also believed that the safety margin of suchtreatments may be better than with an RF-based therapy.

FIG. 5 shows an alternative embodiment of the device in which the firstcatheter 18 and second catheter 20 of the treatment assembly 16 may beinserted alongside an endoscope 12 which may be used to provide forvisualization. Due to the small size of the catheters, this embodimentis feasible.

FIGS. 6A to 6C illustrate an example for a placement procedure for theassembly for the treatment of a body lumen such as the esophagus ES. Thecatheters may be inserted simultaneously or separately through theworking channel of the endoscope 12. In one example, the larger firstcatheter 18 may be inserted first followed by insertion of the secondcatheter 20 within the lumen of the first catheter 18. Once both singleor multi-lumen balloon catheters have been inserted and after theendoscope 12 has been advanced through the esophagus ES and intoproximity to the tissue treatment region, the distal balloon 24 may beadvanced to define the distal end of the treatment area and inflated(e.g., with chilled, room or body temperature fluid) while undervisualization through the endoscope 12, as shown in FIG. 6A. Theendoscope 12 may then be pulled back until the proximal end of thedesired treatment area has been identified and the proximal balloon 22may be slid over the shaft of the second catheter 20 and inflated (e.g.,with chilled, room or body temperature fluid) at a site just proximal tothe most proximal portion of the lesion, as shown in FIG. 6B.

With the treatment area 40 now enclosed by these balloons, an optionalpressure capsule 42 (e.g., solid state, piezoelectric or other pressuresensing method) may be inflated and the treatment may proceed, as shownin FIG. 6C. The treatment session then exposes the lumen or body cavityto fluid pressurized to a positive pressure in the range of, e.g., 5-100cmH2O (although this pressure may be maintained at a level below aninflation pressure of the inflation balloons) at temperatures between,e.g., 50 and 100 degrees Celsius, for a period of, e.g., 1 second to 10minutes. Additionally and/or alternatively, the treatment area 40 may belavaged for a period of time with an anesthetic (e.g., lidocaine orbupivicaine) to reduce pain with the procedure prior to the applicationof thermal energy or other active compounds. Accordingly, ablation maybe accomplished at a consistent depth of, e.g., about 0.5 mm, throughoutthe esophagus ES.

FIGS. 7A to 7C illustrate another example for treatment of an enclosedbody cavity (shown here as a bladder BL). In this example, a singleballoon may be used to effect infusion and extraction of the treatmentfluid. Pressure may be monitored to ensure that the therapy is safe anda relatively lower temperature fluid may be used (e.g., 42-100 C) sothat the entire cavity may see a controlled, uniform thermal load. Theorder or catheter placement may vary as may the sequence for ballooninflation or exposure to active or inactive fluid or vapors in this orany embodiment of the device. As shown in FIG. 7A, an endoscope (orcystoscope) 12 may be inserted into the target organ BL then fluidcatheter 20 may be advanced into the lumen. With the endoscope 12inserted and occlusion balloon inflated 24 (e.g., with unheated fluid)to seal the organ, a pressure sensor 42 may also be optionally inflatedto measure pressure, as shown in FIG. 7B. Optionally, an anesthetic orpre-treatment medication may be delivered into the bladder BL, if sodesired. Then, a high or low temperature fluid 80 may be circulatedwithin the bladder BL under pressure adequate to safely distend theorgan to ensure complete treatment, as shown in FIG. 7C.

FIGS. 8A to 8C illustrate another example for treatment where the use afluid lavage to prepare the treatment area (here shown as the bladderBL) may be accomplished prior to application of thermal (or cooling)energy and/or active compounds. As previously described, the endoscope12 and catheter 20 may be introduced into the bladder BL andsubsequently sealed with the occlusion balloon 24, as shown in FIGS. 8Aand 8B. Preparation of the treatment area may involve use of ananesthetic to decrease pain during therapy or the use of an arterialconstrictor to reduce blood flow to the organ or lumen. Alternatively,other pre-treatment fluids 82 may include, e.g., anesthetic, vascularconstrictor, chilled fluid, active component antidote, etc. Thepre-treatment fluid 82 may be evacuated (or left within the bladder BL)and the lavage with the treatment fluid 80 may be introduced into thebladder BL for treatment, as shown in FIG. 8C.

Alternatively, the pre-treatment fluid 82 may also be chilled or heated)to cool (or warm) the lumen or organ prior to treatment so that thethermal (or cooling) energy may be applied to the internal surface ofthe lumen or body cavity with minimal transmission or conduction of theelevated (or cooling) temperatures to the submucosal tissues or tissueslining the body organ or lumen). Utilizing the pre-treatment of the areamay avoid damage to the underlying tissues to thereby avoid many of thecomplications of therapy. For example, strictures and/or stenosis (ortightening) of the tissue can be avoided by controlling the depth ofpenetration which may be controlled by pre-treating the area with achilled fluid so that the submucosa can absorb significant amounts ofheat without reaching damaging temperatures.

The depth of penetration may also be controlled through the use of alower temperature fluid for thermal ablation so that the submucosa cancool itself with its robust vascular circulation (which is less robustin the mucosa and epithelium). In the event that an active compound isused, as well, an antidote to this compound may be delivered to thepatient (either systemically or as a local pre-treatment) so that theunderlying tissues and submucosa are not damaged. One example of this isthe use of powerful antioxidants (systemically or locally) prior tolavage of the esophagus with, e.g., methotrexate. The methotrexate mayhave a powerful effect on the tissues to which it is directly exposed inthe lumen or body cavity, but the anti-oxidants may prevent deeperpenetration of the methotrexate. The neutralizing compound may also beplaced within the balloon or in the lumen of surrounding lumens or bodycavities to prevent exposure of these areas in the event of balloonrupture.

FIG. 9 shows another example where the distal occlusion member may beconfigured into an umbrella-like element 90 which may be expanded in thestomach ST and placed over a tissue region which is typically difficultto occlude by a balloon. For instance, such a shape may allow forablation of the lower esophageal sphincter LES at the gastroesophagealjunction (or other sphincter region if used elsewhere). The expandable,umbrella-like structure 90 may form a firm seal at this site whileallowing the ablation fluid (hot or cold) to contact the entiregastroesophageal junction. Once expanded, the umbrella-like element 90maybe held firmly against the stomach ST by traction on the endoscope 12or by a tensioning element, on the catheter and balloon itself.

In addition, this element 90 may optionally incorporate a biased orspring-loaded element or other external force mechanism to providesteady pressure and a firm seal against the stomach lining. Alternativestructures may also incorporate a more complex, nitinol cage (or otherrigid material) connected by a thin, water-tight film. For example,nitinol may be used to decrease the overall profile of the obstructionelement and increase its strength and durability.

FIG. 10 shows another example which utilizes an endoscopic balloonsheath utilized as a distal occluder allowing for exposure and treatmentof the distal gastroesophageal junction. In this embodiment, the secondcatheter 20 may have a distal occlusion balloon 100 which may be passedthrough the working channel of the endoscope 12 or through a channelincorporated into the balloon sheath itself (outside of the actualendoscope). Once expanded into an enlarged shape, the balloon 100 may beretracted to fit entirely over the lower esophageal junction LES to formthe distal seal by traction on the endoscope 12 or by a tensioningelement on the catheter and balloon itself. This gastric occlusionballoon may allow for exposure of the gastroesophageal junction whilepreventing fluid flow into the stomach ST. The balloon 22 may beconfigured to be saddle-shaped, circular, wedge-shaped, etc. It may alsobe self-expanding and non-inflatable.

Additionally, the proximal balloon 22 may be configured to be part ofsheath that is placed over the tip of the endoscope 12 or it may beformed directly upon the endoscope tip itself. An inflation lumen mayrun inside the endoscope 12 or it may run alongside the endoscope 12 ina sheath or catheter. The balloon sheath may also incorporate atemperature sensor, pressure sensor, etc. Moreover, the proximalocclusion balloon 22 may optionally incorporate a temperature orpressure sensing element for the therapy and it may be positioned eitherthrough the working channel(s) of the endoscope 12 or alongside theendoscope 12 within the endoscopic balloon sheath.

In yet another embodiment, in order to reduce the risks associated withfluid flow and lavage, a fluid or gel may be infused into the esophagusbetween the balloons then heated or frozen in situ in order to providethe desired ablative effect without circulating any fluid or gel. In oneexample of this configuration, a gel may be infused into the esophagusand pressurized to a safe level (e.g., 30-100 mmHg) which may be thenrapidly chilled using, for example, a compressed gas and/or a Peltierjunction-type cooling element. The gel may freeze at a temperature belowthat of water and allow for rapid transmission of the ablativetemperature to the tissues being treated. This gel may also be a liquidwith a freezing point below that of water in which case the treatmentzone may be lavaged with this fluid prior to treatment to remove freewater and prevent crystal formation during therapy. Once the therapy hasbeen completed, the gel or liquid may be removed or left in theesophagus to be passed into the stomach. In the event that a Peltiercooling or heating element is used, the polarity may be reversed oncetherapy is complete in order to reverse the temperature and terminatethe ablation session.

The distance from the lower end of the distal most portion of thecatheter can be on the order of about 150 mm. The distance between theproximal and distal balloons are adjustable by the operator but can beadjusted, e.g., from as small as 0 mm to as large as 25 cm. Thetreatment zone may have a range of, e.g., 3 to 15 cm.

In yet an additional embodiment, an energy generator (e.g., a RFelectrode or hot wire or other energy source) may be advanced into thetreatment area in a protective sheath (to prevent direct contact withbody tissues) and energy may be applied to the treatment fluid to heatit to the desired temperature. Once the fluid is adequately heated andenough time has passed to achieve a controlled ablation, the fluid maythen be evacuated or neutralized with the influx of colder fluid. Thisembodiment would allow for a very low-profile design and would notrequire any fluid heating element outside of the body.

In another variation, the cavity or lumen may be exposed to the hotwater at a temperature of less than, e.g., 100 degrees Celsius, butgreater than, e.g., 42 degrees Celsius, to allow for easier control ofthe treatment due a longer treatment period. Ranges for optimalhyperthermic treatment include temperatures between, e.g., 42 and 100 Cand exposure periods ranging from, e.g., 15 seconds to 15 minutes. Inthis embodiment, treatment may be effected with an active (e.g.,Methotrexate) or inactive fluid at a temperature of, e.g., 90 degrees C.for a period of e.g., 5-60 seconds, depending on the depth ofpenetration desired.

FIG. 11 shows another example of an endoscopic balloon sheath which maybe used to provide proximal occlusion of the treatment area 40 and mayhouse one or more of the temperature and pressure sensors. Thisvariation may incorporate a stirring/agitating or recirculationmechanism 110 incorporated into the device which may actuated within thetreatment area 40 once the treatment fluid has been introduced to allowfor even cooling/heating. The distal occlusion balloon 100 may beinflated within the stomach ST and pulled proximally with controlledtraction against the gastric portion of the lower esophageal sphincterLES, as previously described.

In this example, a chilled fluid lavage (or vapor infusion) may then beinitiated and the tissue ablated via freezing. A pre-treatment lavage,e.g., a hypertonic, hyperosmotic saline solution, may be introduced withabove freezing temperatures followed by a sub-zero temperature lavage toablate the tissues within the treatment area 40. The hypertonic,hyperosmotic fluid may achieve temperatures down to, e.g., −40 degreesC., without creating ice crystals in the treatment area 40 due to thepre-treatment lavage removing any free water. The treatment fluidfollowing the pre-treatment lavage may have temperatures of, e.g., −2degrees C. to −40 degrees C., for ablation or more particularly atemperature range of, e.g., −5 degrees C. to −20 degrees C. Thistemperature range may allow for freezing and crystal formation in theexposed tissues without damaging the underlying submucosa (which isprotected by the circulation of body temperature blood that preventsfreezing). This temperature range can also be easily achieved withhypersalination of aqueous fluid using sodium chloride and may inhibitany undesired damage to tissues with brief contact. Also, the use of aheavily salinated or other sub-zero solution lavage may provide optimalsealing of the occluding balloons in that any sub-zero temperaturesoutside of the pre-lavaged treatment zone may form an impaction of icecrystals and prevent any further fluid flow outside of the treatmentzone. This hypersalinated water solution is but one freezing solution,though, and any aqueous or non-aqueous fluid or vapor that can beinfused and extracted at this temperature could be used. Alternatively,cryoablative fluid can simply be formed by cooling ethanol or anotheraqueous or lipophilic fluid with subzero cooling temps with compressedgas or dry ice. In another alternative, compressed CO₂ or dry ice may beintroduced into the fluid (e.g., ethanol, butylenes glycol, propyleneglycol, etc) to cool it to, e.g., −50 degrees C. or below.

The use of a subzero solution within this range may also allow for finecontrol of the treatment depth as tissue damage would not begin to occuruntil a temperature differential of about 37 degrees C. is achieved(assuming, a body temperature of 37° C.), but once this threshold isreached tissue damage occurs rapidly due to ice crystal formation. Incontrast, tissue damage is on a continuous spectrum with hyperthermiaand damage may begin to occur at a temperature differential of, e.g., 5degrees C. Thus, the ability of the vasculature to protect theunderlying tissues from damage is greatly reduced due to the smalldifference between the temperature of protective blood versus thetemperature of the ablating fluid. With hypothermic lavage, theprotective blood may differ by, e.g., 37 degrees C., in temperature andmay thus allow for control of ablation depth based on the temperature ofthe fluid lavage and the time of exposure.

Although illustrated esophageal therapy, this therapy could be used inany body cavity/lumen for therapeutic purposes including, but notlimited to, gastrointestinal therapy, stomal tightening (e.g., postbariatric surgery), urogynecologic uses (treatment of cervicalpre-cancers or cancers, endometrial lining treatment, stressincontinence therapy), prostate therapy, intravascular therapy (e.g.,varicose veins) or treatment of any other body cavity/lumen. In theevent that an entire body cavity is being treated (e.g., the entireuterus) a single balloon system may suffice to exclude the entirecavity. The fluid cycling, or dwell may then be accomplished with use ofa pressure-controlled exposure of the cavity or lumen.

FIGS. 12A and 12B show another example of how the system may beintroduced into, e.g., a uterus UT, through the cervix for treatment viathe lavage catheter 20. In this example, the catheter 20 may have adiameter of about, e.g., 8 mm, or in other examples, a diameter ofabout, e.g., less than 6 mm. Infusion of the lavage fluid may fullydistend or partially distend the uterine walls. Optionally, catheter 20may incorporate a tip 120 to perform one or more functions including,e.g., an expandable cage or scaffold to prevent direct exposure of acryoprobe to the tissue walls of the uterus UT, an agitator orrecirculator to ensure even distribution of cryoablation effect, etc. Aspreviously described, the system may be used with lavage or withinfusion then cryoprobe chilling of fluid. In an alternate embodiment,infusion of an antifreeze fluid and insertion of the cryoprobe may bedone separately with chilling of the anti-freeze done after thecryoprobe insertion.

In this and other examples, the therapy may be guided bytime/temperature tracking or visualization (e.g., hysteroscope,endoscope, ultrasound, etc.). Pressure may be regulated by a pressuresensor in line with the infusion or extraction lumen or a dedicatedpressure lumen in a multi-lumen catheter. Additionally, pressure mayalso be regulated by limiting infusion pressure (e.g., height ofinfusion bag, maximum pressure of infusion pump, etc.). Any organ, bodycavity or lumen may be treated using the described lavage and/orinfusion/cryoprobe technique described here for the uterus.

In yet another example, the system may employ a thermally conductivefluid having a thermal conductivity greater than that of saline. Thisthermal conductivity may help to ensure that the fluid within the bodycavity or lumen is at the same temperature throughout even withoutagitation or lavage. Such a fluid may be used with the fluid lavageand/or the fluid infusion followed by application of a cryoprobe. Theimproved thermal conductivity may be achieved via a variety of differentoptions including, but not limited to, choice of a thermally conductivefluid or gel, addition of thermally conductive compounds to the fluid orgel (e.g., metals or metal ions, etc.) and/or agitation of the fluidwithin the cavity to help achieve equilibration of the temperature.

Additionally, the fluid may be infused as a fluid or gel until a setpressure is achieved. The cryoprobe may then be introduced into the bodycavity/lumen and heat may be withdrawn from the fluid/gel. Prior to orin concert with the achievement of a cryotherapeutic (ablative ornon-ablative) temperature, the fluid or may form a gel or solid. Thismay be utilized such that fluid or gel within the cavity may be trappedwithin the target lumen or body cavity with its change in viscosity orstate thereby preventing leakage of the fluid or gel and unwantedexposure of adjacent tissues to the cryotherapeutic effect. Due to thehigher thermal conductivity or the gelled or frozen fluid or gel, thecontinued removal of heat from the gelled or frozen mass may be rapidlyand uniformly distributed throughout the body cavity or lumen. Thesolution may also be partially frozen or gelled and then agitated orrecirculated to ensure even greater distribution of the cryotherapeuticeffect. Furthermore, the fluid or gel may be made thermally conductiveby addition of a biocompatible metal or metallic ion. Any metal orconductive material may be used for this purpose such as silver, gold,platinum, titanium, stainless steel, or other biocompatible metals.

While illustrative examples are described above, it will be apparent toone skilled in the art that various changes and modifications may bemade therein. Moreover, various apparatus or procedures described aboveare also intended to be utilized in combination with one another, aspracticable. The appended claims are intended to cover all such changesand modifications that fall within the true spirit and scope of theinvention.

What is claimed is:
 1. A method for treating a body cavity or lumen,comprising: forming a treatment area for treating a tissue region ofinterest by defining the treatment area with one or more inflatablemembers; adjusting a size of the treatment area by translating a firstcatheter relative to a second catheter; introducing a cryoablative agentinto the treatment area such that the tissue region is treated to acontrolled depth by thermal ablation with the cryoablative agent;monitoring a first pressure of the cryoablative agent introduced intothe treatment area; comparing the first pressure against a secondpressure within the one or more inflatable members; and adjusting thefirst pressure to be below the second pressure if the first pressureexceeds the second pressure.
 2. The method of claim 1 wherein forming atreatment area comprises forming the treatment area within a body lumenselected from the group consisting of an esophagus, uterus, respiratorytract, and bladder.
 3. The method of claim 1 wherein forming a treatmentarea comprises inflating the one or more inflatable members via a fluid.4. The method of claim 1 wherein adjusting a size comprises translatingthe first catheter so that a lesion is contained within the treatmentarea.
 5. The method of claim 1 wherein introducing a cryoablative agentcomprises heating or cooling the cryoablative agent prior to introducinginto the treatment area.
 6. The method of claim 1 further comprisingvisualizing via an endoscope while forming a treatment area.
 7. Themethod of claim 1 wherein a temperature of the cryoablative agent isless than −5 degrees C.
 8. The method of claim 1 further comprisingintroducing an additional fluid into the treatment area having atemperature which warms the treatment area.
 9. The method of claim 1further comprising introducing an agent having an active compound withinthe treatment area.